Without limiting the scope of the invention, its background is described in connection with vaccinations. Vaccinations are an effective and cost-efficient means of protecting against infectious agents; however, injecting vaccines using a hypodermic needle is not the most convenient, likable, or safe method of vaccination. The use of hypodermic needles results in significant pain and discomfort to patients, requires trained personnel for administration, and can cause accidental needle-pricks resulting in transmission of blood borne pathogens such as HIV and hepatitis virus. In contrast, oral administration of vaccination is painless, is the most convenient to use, and can result in high patient compliance. It also has the potential to allow self-administration of vaccines and can allow rapid distribution of vaccines to the public in case of pandemics. Furthermore, processing of locally delivered antigens in the gut-associated lymphoid tissues (GALT) can induce strong mucosal immunity in the gut and other distant mucosal surfaces. On the other hand, the systemic delivery of vaccines using hypodermic needles is a poor stimulator of mucosal immunity. Mucosal immunity is important because mucosal surfaces such as the gut-lining and the respiratory epithelium form a major portal of entry for pathogens, and neutralization of pathogens on mucosal surfaces can form a first line of defense. Thus, overall the oral route of a vaccination is not only safer, convenient and painless, but it is also expected to be functionally superior due to the potential of stimulating both the systemic and the mucosal arms of immunity.
Pollen grains have served as delivery vehicles for their naturally-contained genetic material and allergenic proteins throughout the ages and are natural delivery devices for macromolecules the size of proteins and nucleic acids, as well as for smaller molecules. Their surfaces adhere to tissue surfaces and particularly to mucous membranes and remain in contact for prolonged periods of time to release the substances contained therein to the blood stream or circulatory system. For example, U.S. Pat. No. 7,608,270, entitled, “Dosage Form,” discloses a pharmaceutical or dietetic dosage form comprising of effective quantity of an active substance chemically or physically bound to support comprising sporopollenin, or other similar exine coating of spores, of a plant or fungus, optionally with further excipients.
For example, U.S. Pat. No. 7,846,654, entitled, “Uses of Sporopollenin” discloses the use of an exine shell of a naturally occurring spore, or a fragment thereof, as an antioxidant, for instance in a composition or formulation containing an active substance. Also provided is a method for reducing rancidity, or other oxidative degradation, of a substance, composition, or formulation, by encapsulating the substance, composition, or formulation in, or chemically binding it to, or mixing it with, an exine shell of a naturally occurring spore or a fragment thereof. These patents achieved significant removal of plant native proteins not seen in earlier studies and specify that the pollen grain shell must have protein content less than 0.5% of the exine coating. Based on this qualification the inventors of patent ‘a’ and ‘b’ were able to have new patents issued.
For example, U.S. Pat. No. 5,013,552, entitled, “Modified Pollen Grains for Delivering Biologically Active Substances to Plants and Animals,” discloses loaded pollen grains, which are suitable for use as delivery systems for introducing biologically active substances into or on plants and animals. Such pollen grains are suitable to deliver both small and large (macromolecules) molecules. Preferred pollen grains are those that have been defatted and then pre-treated to be free of antigenic materials and that have special surface features that facilitate their attachment to tissue surfaces, particularly to mucous membranes. The most preferred pollen grains are those that have spiny or irregular or fragmented surfaces. Also disclosed are a method of pre-treating the pollen grains to remove antigenic materials; a method of loading the pollen grains with the biologically active material; and a method of incorporating such pre-treated, loaded pollen grains into formulations or dosage forms suitable for introduction into or on a plant or animal body.
For example, U.S. Pat. No. 5,275,819, entitled, “Drug loaded pollen grains with an outer coating for pulsed delivery,” discloses a pulsating release composition comprising natural microspheres, such as pollen grains or spores, into which are loaded a biologically active that is subsequently releasable therefrom in a predetermined location in or on a plant or animal in a series (generally 3 or more) of pulses. The composition comprises a group of substantially similar loaded microspheres coated with multiple barrier layers alternating with multiple active substance layers in a concentric onion-like structure, the barrier layers being slowly soluble to delay release of active substance from the underlying layer thereof until after the pulse of active substance provided by the overlying layer has subsided. In another preferred embodiment, the composition comprises a plurality of loaded microspheres divided into as many fractions as the desired number of pulses, the loaded microspheres in each consecutive fraction being coated with a barrier layer adapted to dissolve consecutively more slowly to delay release of active substance from such fraction until after the pulse of active substance provided by the prior fraction of consecutively more soluble barrier-coated microspheres has subsided. In another aspect of the invention, the active substance-containing bodies in the compositions may be coated with one or a mixture of absorption-promoting enzymes.